Relation of Serum Adiponectin Levels to Number of Traditional Atherosclerotic Risk Factors and All-Cause Mortality and Major Adverse Cardiovascular Events (from the Copenhagen City Heart Study)

Adiponectin exerts anti-inflammatory and antiatherogenic effects and appears to protect against arteriosclerosis. Accordingly, an association between low concentrations of plasma adiponectin and cardiovascular (CV) disease has been demonstrated in several studies. In contrast, elevated plasma adiponectin has been associated with increased mortality and an increasing number of major adverse CV events (MACE). Because of these conflicting results, the true role of adiponectin remains to be elucidated. In the Copenhagen City Heart Study, we prospectively followed up 5,624 randomly selected men and women from the community without CV disease. Plasma adiponectin was measured at the beginning of the study. The median follow-up time was 7.8 years (interquartile range 7.3 to 8.3). The end point was all-cause mortality (n = 801), and the combined end point was MACE, consisting of CV mortality or nonfatal myocardial infarction or ischemic stroke (n = 502). High adiponectin was inversely associated with an increasing number of traditional CV risk factors (p <0.0001). The geometric mean adiponectin concentrations were 10.0 mg/L (95% confidence interval [CI] 9.7 to 10.4) for persons with no CV risk factors present versus 8.1 mg/L (95% CI 7.8 to 8.4) for persons with 4 CV risk factors. After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of death and MACE. The hazard ratio for each increase in adiponectin of 5 mg/L for death and MACE was 1.20 (95% CI 1.14 to 1.27; p <0.0001) and 1.14 (95% CI 1.05-1.23; p <0.0001), respectively. In conclusion, an increasing number of risk factors for CV disease is associated with decreased plasma adiponectin. High plasma adiponectin independently predicted death and MACE in a large community-based population. These results have confirmed the dual expression indicated by previous studies.